Insulin Resistance Predicts Atherogenic Lipoprotein Profile in Nondiabetic Subjects

Flávia De C Cartolano, Gabriela D Dias, Maria C P de Freitas, Antônio M Figueiredo Neto, Nágila R T Damasceno, Flávia De C Cartolano, Gabriela D Dias, Maria C P de Freitas, Antônio M Figueiredo Neto, Nágila R T Damasceno

Abstract

Background: Atherogenic diabetes is associated with an increased cardiovascular risk and mortality in diabetic individuals; however, the impact of insulin resistance (IR) in lipid metabolism in preclinical stages is generally underreported. For that, we evaluated the capacity of IR to predict an atherogenic lipid subfraction profile.

Methods: Complete clinical evaluation and biochemical analysis (lipid, glucose profile, LDL, and HDL subfractions and LDL phenotype and size) were performed in 181 patients. The impact of IR as a predictor of atherogenic lipoproteins was tested by logistic regression analysis in raw and adjusted models.

Results: HDL-C and Apo AI were significantly lower in individuals with IR. Individuals with IR had a higher percentage of small HDL particles, lower percentage in the larger ones, and reduced frequency of phenotype A (IR = 62%; non-IR = 83%). IR individuals had reduced probability to have large HDL (OR = 0.213; CI = 0.999-0.457) and had twice more chances to show increased small HDL (OR = 2.486; CI = 1.341-7.051). IR was a significant predictor of small LDL (OR = 3.075; CI = 1.341-7.051) and atherogenic phenotype (OR = 3.176; CI = 1.469-6.867).

Conclusion: IR, previously DM2 diagnosis, is a strong predictor of quantitative and qualitative features of lipoproteins directly associated with an increased atherogenic risk.

References

    1. Himsworth H. Diabetes mellitus: its differentiation into insulin sensitive and insulin insensitive types. The Lancet. 1936;227:127–130.
    1. Kahn C. R. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes. 1994;43:1066–1084.
    1. Reaven G. M. Insulin resistance: the link between obesity and cardiovascular disease. The Medical Clinics of North America. 2011;95:875–892. doi: 10.1016/j.mcna.2011.06.002.
    1. Ferrannini E. The insulin resistance syndrome. Current Opinion in Nephrology & Hypertension. 1992;1:291–298.
    1. International Diabetes Federation. IDF Diabetes Atlas. 6th. Brussels: International Diabetes Federation; 2014. June 2016, .
    1. Ferrannini E., Haffner S. M., Mitchell B. D., Stern M. P. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia. 1991;34:416–422.
    1. Reaven G. M. Pathophysiology of insulin resistance in human disease. Physiological Reviews. 1995;75:473–486.
    1. Unger R. H. Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. The Journal of the American Medical Association. 2008;299:1185–1187. doi: 10.1001/jama.299.10.1185.
    1. Reaven G. Insulin resistance and coronary heart disease in nondiabetic individuals. Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:1754–1759. doi: 10.1161/ATVBAHA.111.241885.
    1. Li N., Fu J., Koonen D. P., Kuivenhoven J. A., Snieder H., Hofker M. H. Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance? Atherosclerosis. 2014;233:130–138. doi: 10.1016/j.atherosclerosis.2013.12.013.
    1. Mackey R. H., Mora S., Bertoni A. G., et al. Lipoprotein particles and incident type 2 diabetes in the multi-ethnic study of atherosclerosis. Diabetes Care. 2015;38:628–636. doi: 10.2337/dc14-0645.
    1. Garvey W. T., Kwon S., Zheng D., et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003;52:453–462.
    1. MacLean P. S., Vadlamudi S., MacDonald K. G., Pories W. J., Houmard J. A., Barakat H. A. Impact of insulin resistance on lipoprotein subpopulation distribution in lean and morbidly obese nondiabetic women. Metabolism. 2000;49:285–292.
    1. Festa A., Williams K., Hanley A. J., et al. Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study. Circulation. 2005;111:3465–3472. doi: 10.1161/CIRCULATIONAHA.104.512079.
    1. Milech A., Angelucci A. P., Golbert A., Carrilho A. J., Ramalho A. C., Aguiar A. C. Diretrizes da Sociedade Brasileira de Diabetes (2015-2016) São Paulo: A.C. Farmacêutica; 2016. orgnization José Egidio Paulo de Oliveira, Sérgio Vencio.
    1. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry. 1972;18:499–402.
    1. Matthews D. R., Hosker J. P., Rudenski A. S., Naylor B. A., Treacher D. F., Turner R. C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419.
    1. Stern S. E., Williams K., Ferrannini E., DeFronzo R. A., Bogardus C., Stern M. P. Identification of individuals with insulin resistance using routine clinical measurements. Diabetes. 2005;54:333–339.
    1. DeFronzo R. A., Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14:173–194.
    1. Packard C., Caslake M., Shepherd J. The role of small, dense low density lipoprotein (LDL): a new look. International Journal of Cardiology. 2000;74(Supplement 1):S17–S22.
    1. Berneis K. K., Krauss R. M. Metabolic origins and clinical significance of LDL heterogeneity. Journal of Lipid Research. 2002;43:1363–1379.
    1. Diffenderfer M. R., Schaefer E. J. The composition and metabolism of large and small LDL. Current Opinion in Lipidology. 2014;25:221–226. doi: 10.1097/MOL.0000000000000067.
    1. Shah A. S., Davidson W. S., Gao Z., Dolan L. M., Kimball T. R., Urbina E. M. Superiority of lipoprotein particle number to detect associations with arterial thickness and stiffness in obese youth with and without prediabetes. Journal of Clinical Lipidology. 2016;10:610–618. doi: 10.1016/j.jacl.2016.01.007.
    1. Arca M., Pigna G., Favoccia C. Mechanisms of diabetic dyslipidemia: relevance for atherogenesis. Current Vascular Pharmacology. 2012;10:684–686.
    1. Steiner G., Vranic M. Hyperinsulinemia and hypertriglyceridemia, a vicious cycle with atherogenic potential. International Journal of Obesity. 1982;6(Supplement 1):117–124.
    1. von Eckardstein A., Sibler R. A. Possible contributions of lipoproteins and cholesterol to the pathogenesis of diabetes mellitus type 2. Current Opinion in Lipidology. 2011;22:26–32. doi: 10.1097/MOL.0b013e3283412279.
    1. Drew B. G., Rye K. A., Duffy S. J., Barter P., Kingwell B. A. The emerging role of HDL in glucose metabolism. Nature Reviews Endocrinology. 2012;8:237–245. doi: 10.1038/nrendo.2011.235.
    1. Wu L., Parhofer K. G. Diabetic dyslipidemia. Metabolism. 2014;63:1469–1479. doi: 10.1016/j.metabol.2014.08.010.
    1. Adiels M., Olofsson S. O., Taskinen M. R., Borén J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1225–1236. doi: 10.1161/ATVBAHA.107.160192.
    1. Otvos J. D., Jeyarajah E. J., Bennett D. W., Krauss R. M. Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement. Clinical Chemistry. 1992;38(9):1632–1638.
    1. Barter P. J., Puranik R., Rye K. A. New insights into the role of HDL as an anti-inflammatory agent in the prevention of cardiovascular disease. Current Cardiology Reports. 2007;9:493–498.
    1. Sirtori C. R., Calabresi L., Franceschini G., et al. Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the Limone sul Garda study. Circulation. 2001;103:1949–1954.
    1. Rosenson R. S., Brewer H. B., Ansell B., et al. Translation of high-density lipoprotein function into clinical practice: current prospects and future challenges. Circulation. 2013;128:1256–1267. doi: 10.1161/CIRCULATIONAHA.113.000962.
    1. Pirillo A., Norata G. D., Catapano A. L. High-density lipoprotein subfractions—what the clinicians need to know. Cardiology. 2013;124:116–125. doi: 10.1159/000346463.
    1. Glomset J. A. The plasma lecithins:cholesterol acyltransferase reaction. Journal of Lipid Research. 1968;9:155–167.
    1. Kontush A., Chapman M. J. Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities. Current Opinion in Lipidology. 2010;21:312–318. doi: 10.1097/MOL.0b013e32833bcdc1.
    1. Tian L., Jia L., Mingde F., et al. Alterations of high density lipoprotein subclasses in obese subjects. Lipids. 2006;41:789–796.
    1. Sacks F. M., Campos H. Clinical review 163: cardiovascular endocrinology: low-density lipoprotein size and cardiovascular disease: a reappraisal. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4525–4532. doi: 10.1210/jc.2003-030636.
    1. Lamarche B., Lemieux I., Després J. P. The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, pathophysiology and therapeutic aspects. Diabetes & Metabolism. 1999;25:199–211.
    1. Hoefner D. M., Hodel D. S., O’Brien J. F., et al. Development of a rapid, quantitative method for LDL subfractionation with use of the quantimetrix lipoprint LDL system. Clinical Chemistry. 2001;47:266–274.
    1. Bonora E., Targher G., Alberiche M., et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23:57–63.
    1. DeFronzo R. A., Tobin J. D., Andres R. The glucose clamp technique: a method for quantifying insulin secretion and resistance. The American Journal of Physiology. 1979;237:E214–E223.
    1. Gayoso-Diz P., Otero-González A., Rodriguez-Alvarez M. X., et al. Insulin resistance index (HOMA-IR) levels in a general adult population: curves percentile by gender and age. The EPIRCE study. Diabetes Research and Clinical Practice. 2011;94:146–155. doi: 10.1016/j.diabres.2011.07.015.
    1. Gayoso-Diz P., Otero-González A., Rodriguez-Alvarez M. X., et al. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study. BMC Endocrine Disorders. 2013;13:p. 47. doi: 10.1186/1472-6823-13-47.
    1. Lee C. H., Shih A. Z. L., Woo Y. C., et al. Optimal cut-offs of homeostasis model assessment of insulin resistance (HOMA-IR) to identify dysglycemia and type 2 diabetes mellitus: a 15-year prospective study in Chinese. PLoS One. 2016;11, article e0163424
    1. McKeigue P. M., Shah B., Marmot M. G. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991;337:382–386.
    1. Banerji M. A., Faridi N., Atluri R., Chaiken R. L., Lebovitz H. E. Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. The Journal of Clinical Endocrinology and Metabolism. 1999;84:137–144. doi: 10.1210/jcem.84.1.5371.

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